The extent of neural regulatory influence on the coronary vasculature following the development of severe cardiac hypertrophy and failure is unknown. Because neural control of the coronary circulation normally exerts a considerable modifying influence on the critical balance between myocardial nutrient supply and metabolic demand, it is important to determine whether this neural influence is altered following the development of cardiac hypertrophy, as well as to ascertain whether further adjustments occur during the progression of overt pump failure. It is proposed to investigate this, utilizing a model of pressure overload right (R) ventricular (V) hypertrophy and failure induced by chronic (4-6 months) pulmonary artery stenosis in conscious dogs. Normal dogs and dogs with RV hypertrophy and failure will be instrumented for the continuous measurement of right coronary artery and iliac artery blood flows, RV regional dimensions and aortic and RV pressures. Discrete measurements of regional myocardial blood flow will be made using the radioactive microsphere technique. Pacing electrodes will be sutured to the right atrium so that heart rate can be held constant. The effects of RV hypertrophy and failure on the integrated reflex responses of these measured variables to combined carotid sinus chemoreceptor stimulation and pulmonary inflation activation (induced by the intra-carotid) injection of minute quantities of nicotine) will be evaluated first in spontaneously ventilating coscious dogs. The selective effects of these reflex stimuli will then be assessed during controlled ventilation in these dogs by the intracarotid injection of nicotine and by mechanical hyper-inflation of the lungs, respectively. The extent to which the autonomic nervous system mediates efferent mechanism(s) responsible for the observed changes in the measured variables in response to these reflex stimuli will also be investigated. Finally, the extent to which sympathetic vasoconstrictor modulation of the coronary vasculature supplying the hypertrophied and failing right ventricle is modified will be evaluated by examining the right coronary vascular response to the intra-coronary injection of an alpha adrenergic agonist and antagonist. These studies will provide the first quantitative information concerning the extent to which neural control of the coronary circulation is altered in the hypertrophied and failing heart.